Computer-Aided Drug Design of Capuramycin Analogues as Anti-Tuberculosis Antibiotics by 3D-QSAR and Molecular Docking

Capuramycin and a few semisynthetic derivatives have shown potential as anti-tuberculosis antibiotics.To understand their mechanism of action and structureactivity relationships a 3D-QSAR and molecular docking studies were performed. A set of 52 capuramycin derivatives for the training set and 13 for the validation set was used. A highly predictive MFA model was obtained with crossvalidated q2 of 0.398, and non-cross validated partial least-squares (PLS) analysis showed a conventional r2 of 0.976 and r2pred of 0.839. The model has an excellent predictive ability. Combining the 3D-QSAR and molecular docking studies, a number of new capuramycin analogs with predicted improved activities were designed. Biological activity tests of one analog showed useful antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Computer-aided molecular docking and 3D-QSAR can improve the design of new capuramycin antimycobacterial antibiotics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Predicted Trans-Acting siRNAs in the Human Brain

Endogenous small non-coding RNAs play pivotal roles in regulating gene expression in eukaryotes. Many studies have investigated the function and molecular mechanism of microRNAs in the development and disease of various organisms via mRNA repression of protein-coding genes. Recent findings indicate microRNAs might trigger the generation of trans-acting small interfering RNAs (ta-siRNAs). The interaction among different types of small RNA molecules reveals an even more complicated and elaborate pattern of RNA regulation during gene expression than previously thought. We developed a method for mining ta-siRNA sequences and evaluated the performance of our novel method using data from Arabidopsis thaliana. Additionally, using small RNA and degradome data for the human brain, we identified 155 small RNAs that satisfied ta-siRNA characteristics. The DRAXIN and ATCAY genes, which are preferentially expressed in the human brain, were predicted to be the targets of 12 potential ta-siRNAs

Synthesis, Characterization and Thermochemistry of Hydrated Sodium Phthalate

Phthalic acid and sodium hydroxide were chosen as the reactants and a product of hydrated sodium phthalate was synthesized by the method of liquid phase synthesis. An X-ray powder diffraction technique, chemical and elemental analyses were applied to characterize the composition and structure of the compound. Low-temperature heat capacities of the substance were measured by a precision automated adiabatic calorimeter over a temperature range from 78 to 366 K. A polynomial equation of the heat capacities as a function of the temperature was fitted by the least-squares method. Based on the fitted polynomial, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated at an interval of 5 K. A reasonable thermochemical cycle was designed on the basis of the Hess law, and the standard molar enthalpies of dissolution for the reactants and products of the designed solid phase reaction in the selected solvents were measured by an isoperibol solution-reaction calorimeter, respectively. In addition, the enthalpy change of the reaction was determined to be Delta(r)H(m)= 29.073 +/- 1.05 kJ.mol(-1) from the data of the above standard molar enthalpies of dissolution. Eventually, the standard molar enthalpy of formation of hydrated sodium phthalate was derived to be -1493.637 +/- 1.11 kJ.mol(-1) by the combination of the enthalpy change of the reaction with other auxiliary thermodynamic quantities

Formation and Emissions of Volatile Organic Compounds from Homo-PP and Co-PP Resins during Manufacturing Process and Accelerated Photoaging Degradation

Volatile organic compounds (VOCs) from polypropylene (PP) seriously restricts the application of PP in an automotive field. Herein, the traceability of VOCs from PP resins during manufacturing process and accelerated photoaging degradation was clarified on basis of an accurate characterization method of key VOCs. The influence of PP structures on changing the accelerated photoaging degradation on the VOCs was systematic. The VOCs were identified by means of Gas chromatography (GC) coupled with both a hydrogen flame ion detector (FID) and a mass spectrometry detector (MSD). Results showed that both the molecular structure of PP and the manufacturing process affected the species and contents of VOCs. In addition, the photoaging degradation of PP resulted in a large number of new emerged volatile carbonyl compounds. Our work proposed a possible VOC formation mechanism during the manufacturing and photoaging process. VOCs from PP resins were originated from oligomers and chain random scission during thermomechanical degradation. However, β scission of alkoxy radical and Norrish tape I reactions of ketones via intermediate transition were probably the main VOCs formation routes towards PP during photoaging degradation. This work could provide scientific knowledge on both the accurate traceability of VOCs emissions and new technology for development of low-VOCs PP composites for vehicle

Online Classification of Contaminants Based on Multi-Classification Support Vector Machine Using Conventional Water Quality Sensors

Water quality early warning system is mainly used to detect deliberate or accidental water pollution events in water distribution systems. Identifying the types of pollutants is necessary after detecting the presence of pollutants to provide warning information about pollutant characteristics and emergency solutions. Thus, a real-time contaminant classification methodology, which uses the multi-classification support vector machine (SVM), is proposed in this study to obtain the probability for contaminants belonging to a category. The SVM-based model selected samples with indistinct feature, which were mostly low-concentration samples as the support vectors, thereby reducing the influence of the concentration of contaminants in the building process of a pattern library. The new sample points were classified into corresponding regions after constructing the classification boundaries with the support vector. Experimental results show that the multi-classification SVM-based approach is less affected by the concentration of contaminants when establishing a pattern library compared with the cosine distance classification method. Moreover, the proposed approach avoids making a single decision when classification features are unclear in the initial phase of injecting contaminants

Effects of Microbial Fertilizer on Soil Fertility and Alfalfa Rhizosphere Microbiota in Alpine Grassland

Chemical fertilizers are gradually being replaced with new biological fertilizers, which can improve the soil and soil microorganisms. In this experiment, leguminous forage (Medicago sativa cv. Beilin 201) was used as the research object. By measuring alfalfa root systems and soil properties and using high-throughput sequencing technology, we investigated the effect of biological (rhizobial) fertilizer at different concentrations on soil fertility and alfalfa rhizosphere microbiota in alpine grasslands. The results demonstrated that the treatment with biofertilizer significantly reduced total nitrogen (TN) and total organic carbon (TOC) content in soils, increased root densities, and significantly increased the number of root nodules in alfalfa. There were differences in the response of rhizosphere microorganisms to different concentrations of biofertilizer, and the treatment with biofertilizer led to pronounced changes in the microbial community structure. The abundance of beneficial bacteria such as Rhizobium, Arthrobacter, and Pseudomonas was significantly increased. The Pearson correlation analysis showed that soil moisture and soil conductivity were significantly positively correlated with the observed richness of rhizosphere microbiota (p < 0.05). Meanwhile, Actinobacteria showed a significantly positive correlation with nitrate, TOC, and TN (p < 0.01). These results indicated that biofertilizers enhanced soil fertility and altered the rhizosphere microbiota of alfalfa in alpine grassland

Effects of Microbial Fertilizer on Soil Fertility and Alfalfa Rhizosphere Microbiota in Alpine Grassland

Chemical fertilizers are gradually being replaced with new biological fertilizers, which can improve the soil and soil microorganisms. In this experiment, leguminous forage (Medicago sativa cv. Beilin 201) was used as the research object. By measuring alfalfa root systems and soil properties and using high-throughput sequencing technology, we investigated the effect of biological (rhizobial) fertilizer at different concentrations on soil fertility and alfalfa rhizosphere microbiota in alpine grasslands. The results demonstrated that the treatment with biofertilizer significantly reduced total nitrogen (TN) and total organic carbon (TOC) content in soils, increased root densities, and significantly increased the number of root nodules in alfalfa. There were differences in the response of rhizosphere microorganisms to different concentrations of biofertilizer, and the treatment with biofertilizer led to pronounced changes in the microbial community structure. The abundance of beneficial bacteria such as Rhizobium, Arthrobacter, and Pseudomonas was significantly increased. The Pearson correlation analysis showed that soil moisture and soil conductivity were significantly positively correlated with the observed richness of rhizosphere microbiota (p p < 0.01). These results indicated that biofertilizers enhanced soil fertility and altered the rhizosphere microbiota of alfalfa in alpine grassland

Molecular imaging-monitored radiofrequency hyperthermia-enhanced intratumoral herpes simplex virus-thymidine kinase gene therapy for rat orthotopic ovarian cancer

Objective To establish the technique of intratumoral combination therapy of radiofrequency hyperthermia (RFH) with herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy for rat ovarian cancers. Material and methods This study consisted of three parts: (1) in vitro experiments to establish the ‘proof of principal’ that combination of RFH and HSV-TK gene therapy has the synergistic effect on human ovarian cancer cells; (2) creation of bioluminescence imaging-detectable rat ovarian cancer model; and (3) in vivo experiments using this rat model to validate the technical feasibility of the combination therapy. Cells and nude rats were divided into four groups: (i) combination therapy (HSV-TK/GCV + RFH); (ii) RFH; (iii) HSV-TK/GCV; and (iv) phosphate-buffered saline (PBS). Data were analyzed using Dunnett t-test or Kruskal–Wallis test. Results Cell proliferation assay demonstrated significantly greater reduction in viable cells with the combination therapy [0.52 (0.43, 0.61)] compared to other treatments [RFH 0.90 (0.84, 0.96), HSV-TK/GCV 0.71 (0.53, 0.88), PBS 1 (1, 1); p < .05]. For 24 rat models with bioluminescence imaging-detectable orthotopic ovarian cancer (n = 6 per group), optical imaging demonstrated significantly decreased relative bioluminescence signal with the combination therapy [0.81 (0.52, 1.08)] compared to other treatments [RFH 3.60 (2.34, 4.86), HSV-TK/GCV 2.21 (1.71, 2.71), PBS 3.74 (3.19, 4.29); p < .001]. Ultrasound imaging demonstrated the smallest relative tumor volume with the combination therapy [0.78 (0.45, 1.11) versus 3.50 (2.67, 4.33), 2.10 (0.83, 3.37), 3.70 (1.79, 5.61); p < .05]. Conclusion The feasibility of intratumoral RFH-enhanced HSV-TK/GCV gene therapy was established on a unique rat model with molecular imaging-detectable orthotopic ovarian cancer